CNS 'New Approaches' Consortium Is Dose Escalating Gliadel Wafers in Brain Tumors

WASHINGTON--A consortium of 11 cancer centers is in the midst of a phaseI dose-escalation study of carmus-tine in brain cancer patients, usingGuilford Pharmaceutical's Gliadel Wafer as the drug delivery vehicle.

The FDA approved the wafer for the treatment of glioblastoma multiformein 1996. It consists of a dime-size biodegradable wafer made of polifeprosan20 impregnated with carmustine (BiCNU), 3.9%. Seven or eight wafers areplaced in the cavity created by a tumor's removal and release the drugas they degrade. Most of the drug is delivered within the first few days.

The New Approaches to Brain Tumor Therapy (NABTT) CNS Consortium undertookthe BiCNU escalation trial, in part, because recent animal data suggesta 20% wafer is much more effective than the 3.9% wafer now in use.

The NABTT recently completed testing a 6.5% BiCNU wafer and has beencleared by its monitoring committee to begin a trial of a 10% BiCNU wafer.

Eventually the team hopes to reach 20% BiCNU, project leader StuartA. Grossman, MD, of the Johns Hopkins Oncology Center, said at a congressionalbriefing sponsored by the National Coalition for Cancer Research (NCCR).

Other NABTT Trials

In its first drug test, the NABTT found that the standard dose of paclitaxel(Taxol), when given to brain tumor patients, failed to cause normal sideeffects or offer any real benefit. It turned out, Dr. Grossman said, thatantiseizure medications taken by the patients speeded up the liver's abilityto clear paclitaxel.

In another test, the group found that an investigational drug, 9-amino-camptothecin,did not cause the expected side effects in patients taking anticonvulsantswhen given at a dose of 850 µg/m²/day for three days, the doserecommended by the National Cancer Institute.

As a result, the NABTT has dose escalated this drug in patients takinganticonvulsants to 1776 µg/m²/day for three days.

"Maybe the reason these brain tumors have been so hard to treatis that the drugs have never had a fair trial in patients on anticonvulsantsbecause of unexpected drug interactions between the chemotherapy drug andthe anticonvul-sants," Dr. Grossman said.